The Neuropathology Core provides tissue diagnoses of Alzheimer's disease (AD), and links the clinical studies with basic research. The diagnostic protocol integrates components of the CERAD program and parameters recommended by the NIA-Reagan Institute Workshop Group. The Core plays an integral role in project designs, serving a total of 58 investigators during the current granting period: more than 66 funded projects yielded a large body (>80) of publications. Participants included investigators at USC and four other Southern California institutions, in industry, and in California State and NIA-sponsored ADC's. The core now propose to sever three R01-proposals intrinsic to this application, and a variety of other funded, multi-investigator projects including effects of estrogenic hormones, Abeta vascular transport in the CNS, and individual studies encompassing the effects of AD on basic cellular and neural system functions. Tissues are primarily obtained from patients enrolled in the USC Clinical Core. The patient population draws from three groups: 1) those with probable AD, after exclusion of other dementing diseases, 2) other neurodegenerative disease controls, including Lewy body diseases and fronto-temporal and other lobar dementias, and 3) neurologically normal controls. A twenty-four hour autopsy service obtains CNS and somatics CNS and somatic tissues and is a critical factor in minimizing post-mortem delay. This system insures high- fidelity preparations for biochemistry, molecular biology, genetic analysis and viable tissue cultures. A key feature is that tissue preparations are tailored to special protocols with reliable neuroanatomical dissections performed at autopsy. Our database includes clinical data, neuropathology, diagnosis, tissue inventory and allocation. This database will potentially link clinical and autopsy findings to research data obtained in the participating laboratories.